TRAMADOL/PARACETAMOL KRKA 37.5 mg/325 mg FILM-COATED TABLETS

Introduction

Prospective:patient information

Tramadol/Paracetamol Krka 37.5 mg/325 mg film-coated tablets EFG

tramadol hydrochloride/paracetamol

Read the entire prospectus carefully before starting to take this medication, as it contains important information for you.

• Keep this prospectus, as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• This medication has been prescribed to you only, and you should not give it to others, even if they have the same symptoms as you, as it may harm them.

• If you experience side effects, consult your doctor or pharmacist, even if they are not listed in this prospectus. See section 4.

Contents of the prospectus

1. What is Tramadol/Paracetamol Krka and what is it used for
2. What you need to know before starting to use Tramadol/Paracetamol Krka
3. How to take Tramadol/Paracetamol Krka
4. Possible side effects
   1. Storage of Tramadol/Paracetamol Krka
   2. Package contents and additional information

1. What is Tramadol/Paracetamol Krka and what is it used for

Tramadol/Paracetamol Krka is a combination of two analgesics, tramadol and paracetamol, which work together to relieve your pain.

Tramadol/Paracetamol Krka is indicated for the symptomatic treatment of moderate to severe pain, provided that your doctor considers the combination of tramadol and paracetamol necessary.

Tramadol/Paracetamol Krka should be taken by adults and adolescents over 12 years of age.

2. What you need to know before starting to use Tramadol/Paracetamol Krka

Do not take Tramadol/Paracetamol Krka

• If you are allergic to tramadol hydrochloride, paracetamol, or any of the other components of this medication (listed in section 6).
• If you are suffering from acute intoxication with alcohol, sleeping pills, analgesics, or other psychotropic medications (medications that affect mood and emotions).
• If you are taking monoamine oxidase inhibitors (MAOIs) (certain medications used to treat depression or Parkinson's disease) or have taken them in the last 14 days before treatment with this medication.
• If you have severe liver disease.
• If you have uncontrolled epilepsy.

Warnings and precautions

Consult your doctor before starting to take Tramadol/Paracetamol Krka if you:

• are taking other medications that contain paracetamol or tramadol;
• have liver problems or liver disease, or if you notice that your eyes or skin turn yellow. This may be indicative of jaundice or problems with your bile ducts;
• have kidney problems;
• have severe breathing difficulties, such as asthma or severe lung problems;
• are epileptic or have had seizures or convulsions;
• suffer from depression and are taking antidepressants, as some may interact with tramadol (see "Taking Tramadol/Paracetamol Krka with other medications");
• have recently suffered a head injury, shock, or severe headaches associated with vomiting;
• are dependent on any other medication used for pain relief, such as morphine;
• are taking other medications for pain relief that contain buprenorphine, nalbuphine, or pentazocine;
• are going to be anesthetized. Tell your doctor or dentist that you are taking tramadol/paracetamol.

During treatment with tramadol/paracetamol, inform your doctor immediately if:

If you have severe diseases, such as severe kidney failure or sepsis (when bacteria and their toxins circulate in the blood, causing damage to organs), or if you suffer from malnutrition, chronic alcoholism, or are also taking flucloxacillin (an antibiotic). A severe disease called metabolic acidosis (an anomaly in the blood and fluids) has been reported in patients in these situations when paracetamol is used at regular doses for a prolonged period or when paracetamol is taken with flucloxacillin. The symptoms of metabolic acidosis may include: severe breathing difficulties with deep and rapid breathing, drowsiness, feeling of discomfort (nausea) and vomiting.

Tolerance, dependence, and addiction

This medication contains tramadol, which is an opioid medication. Repeated use of opioids can make the medication less effective (you get used to it, which is known as tolerance). Repeated use of tramadol/paracetamol can also lead to dependence, abuse, and addiction, which can result in a potentially fatal overdose. The risk of these side effects may increase with a higher dose and longer duration of use.

Dependence or addiction can make you feel like you no longer control the amount of medication you need to take or how often you need to take it.

The risk of becoming dependent or addicted varies from person to person. You may have a higher risk of becoming dependent or addicted to tramadol/paracetamol if:

• You or someone in your family has abused or been dependent on alcohol, prescription medications, or illegal drugs ("addiction")
• You are a smoker
• You have ever had problems with your mood (depression, anxiety, or a personality disorder) or have been treated by a psychiatrist for other mental illnesses

If you notice any of the following signs while taking tramadol/paracetamol, it could be a sign that you have become dependent or addicted:

• You need to take the medication for longer than advised by your doctor
• You need to take more than the recommended dose
• You use the medication for reasons other than those prescribed, for example, "to calm down" or "to sleep"
• You have repeatedly tried and failed to stop or control the use of the medication
• When you stop taking the medication, you feel unwell, and you feel better when you take it again ("withdrawal effect")

If you observe any of these signs, talk to your doctor so that they can indicate the best course of treatment for you, including when it is appropriate to stop taking it and how to do so safely (see section 3, If you interrupt treatment with tramadol/paracetamol).

Respiratory disorders related to sleep

Tramadol/Paracetamol Krka contains an active ingredient that belongs to the group of opioids. Opioids can cause respiratory disorders related to sleep, such as central sleep apnea (shallow or paused breathing during sleep) and sleep-related hypoxemia (low oxygen levels in the blood).

The risk of experiencing central sleep apnea depends on the dose of opioids. Your doctor may consider reducing the total dose of opioids if you experience central sleep apnea.

There is a weak risk that you may experience a serotonin syndrome that can occur after taking tramadol in combination with certain antidepressants or tramadol alone. Consult a doctor immediately if you present any of the symptoms related to this serious syndrome (see section 4 "Possible side effects").

Tramadol is transformed in the liver by an enzyme. Some people have a variation of this enzyme, and this can affect each person differently. In some people, sufficient pain relief may not be achieved, while others are more likely to experience serious side effects. If you notice any of the following side effects, you should stop taking this medication and consult a doctor immediately: slow or shallow breathing, confusion, drowsiness, constricted pupils, general discomfort or vomiting, constipation, lack of appetite.

If you have had any of these problems in the past while taking tramadol/paracetamol, please inform your doctor. They will decide whether you should continue taking this medication.

Children and adolescents

Use in children with respiratory problems

Tramadol is not recommended for use in children with respiratory problems, as the symptoms of tramadol toxicity can worsen in these children.

Consult your doctor if you experience any of the following symptoms while taking this medication:

Extreme fatigue, lack of appetite, severe abdominal pain, nausea, vomiting, or low blood pressure. This may indicate that you have adrenal insufficiency (low cortisol levels). If you present any of these symptoms, contact your doctor, who will decide whether you need to take a hormonal supplement.

Other medications and Tramadol/Paracetamol Krka

Tell your doctor or pharmacist if you are taking, have recently taken, or may need to take any other medication.

Important:this medication contains paracetamol and tramadol. Inform your doctor if you are taking any other medication that contains paracetamol or tramadol, so that you do not exceed the maximum daily dose.

Do nottake this medication with monoamine oxidase inhibitors (MAOIs) (see section "Do not take Tramadol/Paracetamol Krka").

It is not recommended to use Tramadol/Paracetamol Krkaif you are being treated with:

• carbamazepine (a medication normally used to treat epilepsy or certain types of pain, such as intense facial pain called trigeminal neuralgia),
• buprenorphine, nalbuphine, or pentazocine (opioid analgesic). Pain relief may be reduced.

Tell your doctor or pharmacist if you are taking:

• flucloxacillin (an antibiotic), due to a serious risk of blood and fluid anomalies (called metabolic acidosis) that require urgent treatment (see section 2).

The risk of side effects increases if you also use:

• triptans (for the treatment of migraines) or selective serotonin reuptake inhibitors, "SSRIs" (for the treatment of depression). If you experience confusion, agitation, fever, sweating, uncoordinated limb or eye movements, or diarrhea, you should call your doctor.
• other analgesics such as morphine and codeine (also cough medications), baclofen (muscle relaxant), certain medications to lower blood pressure, or medications for the treatment of allergies. You may feel drowsy or dizzy. If this occurs, consult your doctor.
• The concomitant use of Tramadol/Paracetamol Krka and sedative medications such as benzodiazepines or related medications increases the risk of drowsiness, respiratory difficulties (respiratory depression), coma, and can be potentially fatal. For this reason, concomitant use should only be considered when no other treatment options are possible. However, if your doctor prescribes this medication with sedative medications, you should limit the dose and duration of concomitant treatment. Inform your doctor of all sedative medications you are taking and strictly follow your doctor's recommended dosage. It may be helpful to inform your friends and family about the signs and symptoms indicated above. Inform your doctor if you experience any of these symptoms.
• medications that can cause seizures (attacks), such as certain antidepressants or antipsychotics. The risk of having a seizure may increase if you take this medication at the same time. Your doctor will tell you if tramadol/paracetamol is suitable for you.
• certain antidepressants. Tramadol/paracetamol may interact with these medications, and you may experience a serotonin syndrome (see section 4 "Possible side effects").
• warfarin or phenprocoumon (a medication used to prevent blood clots). The effectiveness of these medications may be altered, and there is a risk of bleeding. You should inform your doctor immediately of any prolonged or unexpected bleeding.
• gabapentin or pregabalin to treat epilepsy or pain due to nerve problems (neuropathic pain).

The effectiveness of Tramadol/Paracetamol Krka may be altered if you also use:

• metoclopramide, domperidone, or ondansetron (medications for the treatment of nausea and vomiting),
• cholestyramine (a medication that reduces cholesterol in the blood).

Your doctor will indicate which medications are safe to use with tramadol/paracetamol.

Taking Tramadol/Paracetamol Krka with food and alcohol

Tramadol/paracetamol may make you feel drowsy. Alcohol may make you feel more drowsy, so it is recommended not to drink alcohol while taking this medication.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medication.

Because this medication contains tramadol, it is not recommended to take it during pregnancy or breastfeeding. If you become pregnant during treatment with tramadol/paracetamol, consult your doctor before taking the next tablet.

Breastfeeding

Tramadol is excreted in breast milk. For this reason, you should not take this medication more than once during breastfeeding, or alternatively, if you are taking this medication more than once, you should interrupt breastfeeding.

Fertility

Based on human experience, tramadol is not considered to affect female or male fertility. There is no available data on the influence of tramadol and paracetamol on fertility.

Ask your doctor or pharmacist for advice before taking any medication.

Driving and using machines

Tramadol/paracetamol may make you feel drowsy, and this can affect your ability to drive or use tools and machines safely.

Tramadol/Paracetamol Krka contains sodium

This medication contains less than 1 mmol of sodium (23 mg) per tablet; this is, essentially "sodium-free".

3. How to take Tramadol/Paracetamol Krka

Follow the administration instructions for this medication exactly as indicated by your doctor. If in doubt, consult your doctor or pharmacist again.

Before starting treatment and regularly during treatment, your doctor will explain what you can expect from the use of tramadol/paracetamol, when and for how long you should take it, when you should contact your doctor, and when you should stop taking it (see also section 2).

You should take tramadol/paracetamol for the shortest possible time.

It is not recommended to use this medication in children under 12 years of age.

The dose should be adjusted according to the intensity of the pain and your individual sensitivity. Normally, the lowest possible dose that produces pain relief should be used.

Unless your doctor prescribes otherwise, the recommended starting dose for adults and adolescents over 12 years of age is 2 tablets.

If necessary, you can increase the dose, as recommended by your doctor. The shortest interval between doses should be at least 6 hours.

Do not take more than 8 tablets per day.

Do not take tramadol/paracetamol more frequently than indicated by your doctor.

Elderly patients

In elderly patients (over 75 years of age), the excretion of tramadol may be delayed. If this is your case, your doctor may recommend prolonging the dosing intervals.

Patients with severe hepatic or renal impairment/dialysis

Patients with severe renal and/or hepatic impairment should not take this medication.

If your impairment is mild or moderate, your doctor may recommend prolonging the dosing interval.

Administration route

The tablets should be administered orally.

They should be swallowed whole with sufficient liquid. The tablets should not be broken or chewed.

If you think the effect of this medication is too strong (e.g., you feel very drowsy or have difficulty breathing) or too weak (e.g., you have inadequate pain relief), contact your doctor.

If you take more Tramadol/Paracetamol Krka than you should

In these cases, contact your doctor or pharmacist immediately, even if you feel well. There is a risk of serious liver damage that may only become apparent later.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicological Information Service, phone 91 562 04 20, indicating the medication and the amount taken.

If you forget to take Tramadol/Paracetamol Krka

If you forget to take a dose of this medication, it is likely that the pain will return. Do not take a double dose to make up for the missed doses; simply continue taking the tablets as usual.

If you interrupt treatment with Tramadol/Paracetamol Krka

Do not stop taking this medication suddenly unless your doctor tells you to. If you want to stop taking your medication, talk to your doctor first, especially if you have been taking it for a long time. Your doctor will advise you when and how to stop taking it, which can be done by gradually reducing the dose to reduce the possibility of developing unnecessary side effects (withdrawal symptoms).

If you have any other questions about the use of this medication, ask your doctor or pharmacist.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

Very Common (may affect more than 1 in 10 people):

• nausea,

• dizziness, drowsiness.

Common (may affect up to 1 in 10 people):

• vomiting, digestion problems (constipation, flatulence, diarrhea), abdominal pain, dry mouth,
• itching, increased sweating (hyperhidrosis),
• headache, tremors,
• confusion, sleep disorders, mood changes (anxiety, nervousness, feeling "high").

Uncommon (may affect up to 1 in 100 people):

• increased pulse or increased blood pressure, cardiac rhythm and frequency disorders,

• tingling sensation, numbness or pinching sensation in the limbs, ringing in the ears, involuntary muscle spasms,
• depression, nightmares, hallucinations (hearing, seeing or perceiving something that does not exist in reality), memory loss,
• breathing difficulties,
• difficulty swallowing, blood in the stool,
• skin reactions (e.g., rashes, urticaria),
• increased liver enzyme values,
• presence of albumin in the urine, difficulty or pain when urinating,
• chills, hot flashes, chest pain.

Rare (may affect up to 1 in 1,000 people):

• seizures, difficulties in carrying out coordinated movements, transient loss of consciousness (syncope),

• dependence on the medicine,
• delirium,
• blurred vision, pupil constriction (miosis),
• speech disorders,
• excessive dilation of the pupils (mydriasis).

Very Rare (may affect up to 1 in 10,000 people):

• addiction to the drug.

Unknown Frequency (frequency cannot be estimated from the available data):

• decrease in blood sugar levels (hypoglycemia).

The following recognized adverse effects have been reported by people who have taken medicines containing only tramadol or only paracetamol. However, if you experience any of these symptoms while taking this medicine, you should tell your doctor:

• feeling of dizziness when standing up after lying down or sitting, slowing of heart rate, fainting, changes in appetite, muscle weakness, slower or weaker breathing, mood changes, changes in activity, changes in perception, worsening of asthma.
• taking paracetamol alone or when taken with the antibiotic flucloxacillin may induce a blood and fluid anomaly (metabolic acidosis with high anion gap) when there is an increase in blood plasma acidity.
• taking tramadol/paracetamol with anticoagulants (e.g., phenprocoumon, warfarin) may increase the risk of bleeding. You should inform your doctor immediately about any prolonged or unexpected bleeding.
• in rare cases, skin rashes, which are indicative of allergic reactions that can manifest through sudden swelling of the face and neck, shortness of breath, or a drop in blood pressure and dizziness. If this happens to you, stop treatment and consult your doctor immediately. You should not take this medicine again.

In rare cases, using a medicine like tramadol can create dependence, making it difficult to stop taking it.

In rare cases, people who have been taking tramadol hydrochloride for some time may feel unwell if they suddenly stop treatment. They may feel agitated, anxious, nervous, or trembly. They may be hyperactive, have difficulty sleeping, and have digestive and intestinal disorders. Very few people may also have panic attacks, hallucinations, unusual perceptions such as itching, tingling, and numbness, and ringing in the ears (tinnitus). If you experience any of these symptoms after stopping treatment, please consult your doctor.

Unknown frequency: hiccups.

Serotonin syndrome, which can manifest through changes in mental state (e.g., agitation, hallucinations, coma), and other effects, such as fever, increased heart rate, unstable blood pressure, involuntary muscle contractions, muscle stiffness, lack of coordination, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea) (see section 2 "What you need to know before taking Tramadol/Paracetamol Krka").

In exceptional cases, blood tests may reveal certain abnormalities, such as low platelet count, which can result in nosebleeds or bleeding gums.

Very rare cases of adverse skin reactions have been described for medicines containing paracetamol.

Rare cases of respiratory depression have been reported with tramadol.

Unknown frequency (cannot be estimated from the available data): a serious disease that can make the blood more acidic (called metabolic acidosis) in patients with severe disease using paracetamol (see section 2).

Reporting of Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that is not listed in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Tramadol/Paracetamol Krka

Keep this medicine out of the sight and reach of children.

Store this medicine in a safe and protected place, where other people cannot access it. It can cause serious harm and be fatal for people who have not been prescribed it.

Do not use this medicine after the expiration date stated on the packaging after CAD. The expiration date is the last day of the month indicated.

This medicine does not require special storage conditions.

Medicines should not be disposed of via wastewater or household waste. Deposit the packaging and medicines you no longer need at the SIGRE collection point in your pharmacy. Ask your pharmacist how to dispose of the packaging and medicines you no longer need. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Tramadol/Paracetamol Krka

• The active ingredients are tramadol hydrochloride and paracetamol. Each film-coated tablet contains 37.5 mg of tramadol hydrochloride equivalent to 32.94 mg of tramadol and 325 mg of paracetamol.
• The other ingredients are:

• tablet core:pregelatinized corn starch, sodium starch glycolate (type A), microcrystalline cellulose (E460), and magnesium stearate (E470b).
• coating:hypromellose, titanium dioxide (E171), macrogol 400, yellow iron oxide (E172), and polysorbate 80. See section 2 "Tramadol/Paracetamol Krka contains sodium".

Appearance of Tramadol/Paracetamol Krka and Package Contents

Yellow-brown, oval, slightly biconvex film-coated tablets.

Available in packs of 2 film-coated tablets (blisters of 2 tablets) or 10, 20, 30, 40, 50, 60, 70, 80, 90, and 100 film-coated tablets (blisters of 10 tablets).

Not all pack sizes may be marketed.

Marketing Authorization Holder

KRKA, d.d.,

Novo mesto, Šmarješka cesta 6,

8501 Novo mesto,

Slovenia

Manufacturer

KRKA, d.d.,

Novo mesto, Šmarješka cesta 6,

8501 Novo mesto,

Slovenia

O

TAD Pharma GmbH,

Heinz-Lohmann-Straße 5,

27472 Cuxhaven,

Germany

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

KRKA Farmacéutica, S.L.,

C/ Anabel Segura 10, Pta. Baja, Oficina 1,

28108 Alcobendas, Madrid,

Spain

This medicine is authorized in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:

Date of the Last Revision of this Leaflet:May 2025

Detailed information about this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) (http://www.aemps.gob.es/).